Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Purpose: Conventional gonadal shields are manufactured in standardized sizes and shapes and do not conform to individual testicular contours, causing discomfort. We developed a novel patientspecific gonadal shield using thermoplastic sheets and tested its feasibility through dosimetric evaluations. Methods: During the computed tomography simulation, custom lead shields were fabricated using thermoplastic sheets that were molded to the testicular shape of the patient. The shielding efficacy was evaluated using optically stimulated luminescent dosimeters (OSLDs) for point dose measurements. Results: The thermoplastic sheet was molded to fit closely to the skin with a minimal air gap of approximately 8.4 cm³, providing comfort to the patient during treatment. The patient-specific shield effectively reduced the surface dose from 28 cGy to less than 15 cGy. By combining the OSLDs located in the same row and calculating the mean dose value, a shielding effect was achieved with a maximum dose reduction of 56.1%. Conclusions Customized gonadal shields were successfully created using thermoplastic sheets to minimize patient discomfort during application. However, further improvements in lead shield fabrication are needed to ensure full conformity.

Purpose: This study investigated the dose perturbation according to the size of the sensitive volume in the dosimeter in small-field dosimetry. Methods: The dose profiles with different field sizes were measured using three different dosimeters: the CC13, Razor ion chamber, and Edge solid-state detector. Both the open and wedged beams with different field sizes were employed in the measurement. The profiles were measured in a water phantom at maximum dose depths of 5, 10, and 20 cm. The penumbra and width of the open-beam profiles were compared according to the types of the dosimeters and beam. The dose fall-off between the peak and 20% dose was evaluated for the wedged beam profiles. Results: In the open-beam measurement, the fall-off of the profile was steeper with the Edge detector, which has the smallest sensitive volume. Meanwhile, the dose in the out-of-field region was the smallest with the Edge detector. The widths of the penumbra were 6.10, 4.47, and 4.03 mm for the profile of the 3×3 cm 2 field measured by the CC13 chamber, Razor chamber, and Edge detector, respectively. The width of the profile was not changed even if different dosimeters were used in the measurement. The wedged beam profiles showed more clear peaks at the field edge when a smaller dosimeter was used. Conclusions The results demonstrate the necessity of dosimeters with a small sensitive volume for measuring a small-field beam or a steep dose gradient.

Purpose: This study evaluated various methods for determining the half-value layer (HVL) of kilovoltage (kV) beams produced by the Varian TrueBeam STx on-board imager. By comparing these methods with the standard ionization chamber approach, the study aimed to identify practical solutions for HVL determination and dosimetric characterization of kV beams, particularly in resource-limited settings. Methods: HVLs for kV beams (40–140 kVp) were measured using an Exradin A12 ionization chamber and a Piranha MULTI meter. The ionization chamber measurements adhered to American Association of Physicists in Medicine Task Group 61 guidelines and served as the reference standard. Additionally, HVL values were calculated using two model-based approaches: SpekPy (a Python-based tool) and Monte Carlo (MC) simulations using Geant4 and GATE. The results from these methods were compared to assess consistency and reliability. Results: Deviations across all methods were generally below 4%. At 40 kV, the most significant discrepancies were attributed to lower signal levels from the ionization chamber. The consistency between the model-based methods and experimental measurements demonstrates the reliability of these alternative approaches for HVL determination. Conclusions Although the ionization chamber remains the gold standard, the Piranha MULTI meter and model-based methods, i.e., SpekPy and MC simulations, have shown promise as viable alternatives, especially in resource-constrained settings. These in silico approaches also offer advantages in convenience and accuracy, supporting their potential for broader future applications.

Purpose: Brachytherapy is essential for treating gynecological cancers as it offers precise radiation delivery to tumors while minimizing radiation exposure to surrounding healthy tissues. The Geneva applicator, introduced in 2020 as a replacement for older models like the Utrecht applicator, enhances MRI-based brachytherapy with improved imaging capabilities and more accurate applicator placement. In 2021, updates to non-reimbursement policies in Korea for MRI-based 3D brachytherapy planning further promoted the adoption of advanced techniques such as the Geneva applicator. This study aims to commission the Geneva applicator, focusing on wall thickness, dummy marker positions, and source dwell positions to ensure accurate dose delivery and safety. Methods: The commissioning process involved measuring wall thickness in both the longitudinal and transverse directions for the tandem and lunar-shaped ovoid tubes and comparing thesemeasurements with the manufacturer’s specifications. Dummy marker positions were verifiedusing CT imaging, with a focus on alignment tolerances of ±1 mm. Source dwell positions were planned using the Oncentra treatment planning system, with measurements taken using EBT4 film and analyzed with RIT software. Results: Wall thickness measurements and dummy marker positions were within the specified tolerance ranges, confirming their accuracy. The source dwell positions, measured and analyzedthrough multiple tests, were all within the ±1 mm tolerance, ensuring the applicator’s reliability. Conclusions The Geneva applicator met all standards for safe and effective use in brachytherapy.The use of a 3D-printed holder was crucial for precise alignment and measurement. With updated reimbursement policies in Korea for MRI-based brachytherapy, the Geneva applicator is expected to significantly impact the future of advanced brachytherapy treatments and research.

Herein, we provide a concise review of the critical role of motion management in radiation therapy, with a focus on photon radiation therapy, real-time control of respiratory motion, and image-guided radiation therapy (IGRT) in lung stereotactic body radiation therapy (SBRT). The dynamic nature of human anatomy, particularly in regions prone to movement such as the thoracic and abdominal areas, poses significant challenges in accurately targeting tumors during radiation therapy. This review explores the implications of organ and tumor motion, emphasizing the necessity for precise treatment delivery. We assess the advancements in four-dimensional (4D) imaging techniques such as 4D computed tomography, which provide time-resolved images for enhanced treatment planning. The review highlights various motion management strategies, including motionencompassing methods, respiratory-gating, breath-hold techniques, and real-time tumor tracking, discussing their implementation and impact on treatment efficacy. The role of IGRT in lung SBRT is particularly emphasized, showcasing how real-time imaging and advanced targeting techniques enhance the precision of high-dose radiation delivery while minimizing exposure to surrounding healthy tissues. This comprehensive review aims to underscore the significance of integrating motion management in radiation therapy, highlighting its pivotal role in improving treatment accuracy, reducing toxicity, and ultimately enhancing patient outcomes in cancer care.

Purpose: Accurate operation of the multi-leaf collimator (MLC), a key technology in intensity modulated radiation therapy (IMRT), is essential for safe and optimal radiation treatment. The HalcyonTM linear accelerator has a collimator with low leakage and radiation transmission, making it suitable for IMRT. The limitations of the existing HalcyonTM MLC quality assurance (QA) method were supplemented with a mathematical method, and the results were analyzed. Methods: Electric portal imaging device (EPID) images obtained by performing the MLC QA plan on the HalcyonTM was analyzed using Python. The picket fence tests were performed and compared using the maximum pixel value and mathematical methods. Dose rate, gantry speed, and leaf speed variation plan were performed for dose transmission comparison. Results: For the maximum pixel value, the minimum distance between leaf junctions was 13.86 mm, and the maximum was 16.06 mm. However, for the mathematical method, the minimum and maximum were 14.54 mm and 15.68 mm, respectively. This suggests that setting the peak value to the highest value may cause an error in interpretation due to the limitations of the pixels of the EPID image. Performing QA on the remaining items confirmed that the measured values were within 3% of tolerance. Conclusions The presented analysis method applied to the MLC QA can derive more reasonable and valid values than existing methods, which will help with MLC monitoring by reducing errors in excessive interpretation.

Purpose: Conventional gonadal shields are manufactured in standardized sizes and shapes and do not conform to individual testicular contours, causing discomfort. We developed a novel patientspecific gonadal shield using thermoplastic sheets and tested its feasibility through dosimetric evaluations. Methods: During the computed tomography simulation, custom lead shields were fabricated using thermoplastic sheets that were molded to the testicular shape of the patient. The shielding efficacy was evaluated using optically stimulated luminescent dosimeters (OSLDs) for point dose measurements. Results: The thermoplastic sheet was molded to fit closely to the skin with a minimal air gap of approximately 8.4 cm³, providing comfort to the patient during treatment. The patient-specific shield effectively reduced the surface dose from 28 cGy to less than 15 cGy. By combining the OSLDs located in the same row and calculating the mean dose value, a shielding effect was achieved with a maximum dose reduction of 56.1%. Conclusions Customized gonadal shields were successfully created using thermoplastic sheets to minimize patient discomfort during application. However, further improvements in lead shield fabrication are needed to ensure full conformity.